Receptor research on xenohormone effects of human serum extracts containing the actual mixture of perfluorinated alkyl acids: a short review

Perfluorinated alkyl acids (PFAAs) are used in many household products including food contact materials. Hence, humans are continuously exposed, and the PFAAs are accumulated in human serum with half-lives up to 8.8 years. In humans, high PFAA serum levels have been associated with an increased risk of breast cancer and other adverse health effects such as lower birth weight and longer time to pregnancy which might be related to disruptions of various hormonal systems. For instance, direct cell exposure studies in vitro suggest that some PFAAs can transactivate the estrogen receptor (ER), antagonize the androgen receptor (AR) and has the potential to interfere with TH and AhR functions. Moreover, the PFAAs also showed cellular oxidative stress. Humans are exposed to an array of PFAAs, and the quantity and combination of these PFAAs in human serum differs between individuals. Hence, the toxicological studies of single PFAAs and simple mixtures might be insufficient to predict how the actual mixtures of PFAAs may affect humans. To get a better evaluation of the actual mixture effects, we developed a method to extract the actual mixture of PFAAs from human serum. Preliminary results showed that 17% of the PFAA serum fractions from pregnant women could significantly transactivate the ER, and 94% of the fractions could further increase the transactivity induced by the potent ER ligand 25 pM 17?-estradiol. As part of the international FETOTOX project (http://fetotox.au.dk/), we are currently extracting the actual PFAA serum mixture from 700 pregnant women to further elucidate whether the serum PFAA mixture can transactivate the ER at the levels found in human serum. We suggest that our method can in the future be used to study the actual serum PFAA mixture effects on both steroid hormone actions as well as other hormonal systems e.g. thyroid hormone function. In the current review we will discuss how our recently developed PFAA extraction method might be used in future research to assess the endocrine impact of PFAAs on human health

Levels of Pesticides and Their Metabolites in Wistar Rat Amniotic Fluids and Maternal Urine upon Gestational Exposure.

Concentrations of pesticides and selected metabolites in rat urine and amniotic fluid were determined as biomarker upon oral administration of Wistar rats to two pesticide mixtures consisting of three to five pesticides (bitertanol, propiconazole, cypermethrin, malathion, and terbuthylazine). The pesticides and their metabolites were found in rat amniotic fluid and urine, generally in dose-response concentrations in relation to dosage. The measurement of the substances in the amniotic fluid indicated that the fetus was exposed to the pesticides as well as their metabolites. Moreover, the pesticides detected in urine demonstrated the exposure as well as the ability of the rat to excrete these compounds

Health effects associated with measured levels of contaminants in the Arctic

Published version. Source at http://dx.doi.org/10.3402/ijch.v75.33805 The Human Health Assessment Group has over the past decade recommended that effect studies be conducted in the circumpolar area. Such studies examine the association between contaminant exposure in the Arctic populations and health effects. Because foetuses and young children are the most vulnerable, effect studies are often prospective child cohort studies. The emphasis in this article is on a description of the effects associated with contaminant exposure in the Arctic. The main topics addressed are neurobehavioural, immunological, reproductive, cardiovascular, endocrine and carcinogenic effect. For each topic, the association between exposure and effects is described, and some results are reported for similar studies outside the Arctic

Overview of ongoing cohort and dietary studies in the Arctic

Published version. Source at http://dx.doi.org/10.3402/ijch.v75.33803 This article gives an overview of the ongoing cohort and dietary studies underlying the assessment of population health in the Arctic. The emphasis here is on a description of the material, methods and results or preliminary results for each study. Detailed exposure information is available in an article in this journal, whereas another paper describes the effects associated with contaminant exposure in the Arctic. The cohort descriptions have been arranged geographically, beginning in Norway and moving east to Finland, Sweden, Russia and the other Arctic countries and ultimately to the Faroe Islands. No cohort studies have been reported for Alaska or Iceland

Fertility in four regions spanning large contrasts in serum levels of widespread persistent organochlorines: a cross-sectional study

BACKGROUND: Persistent organochlorine pollutants (POPs) may interfere with reproductive function but direct evidence in humans is very limited. METHODS: Fertility was examined in four regions with contrasting blood levels of POPs. Pregnant women and their partners in Warsaw (Poland), Kharkiv (Ukraine) and Greenland were consecutively enrolled during antenatal visits. Swedish fishermen and their spouses were recruited separately and independently of current pregnancy. Lipid adjusted serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (DDE) were available for both partners. Time to pregnancy interviews were obtained among 2269 women and 798 men provided a semen sample. RESULTS: Inuits had high levels of both POP markers, Swedish fishermen were high in CB-153 but low in DDE, men from Kharkiv were high in DDE and low in CB-153 while men from Warsaw were low in CB-153 and had intermediate DDE levels. Compared to Warsaw couples, fecundability was reduced among couples from Kharkiv [adjusted fecundability ratio (FR) 0.64 (95% CI 0.5-0.8)] and elevated in Swedish fishermen families [FR 1.26 (95% CI 1.0-1.6)]. Adjusted geometric means of sperm counts and morphology did not differ between regions while sperm motility was higher in men living in Warsaw. CONCLUSION: We observed regional differences in time to pregnancy and sperm motility that may be related to regional differences in POP blood levels, but other interpretations are also plausible. In particular, differences in access to safe contraception and in the prevalence of contraceptive failures are most likely to bias comparisons of time to pregnancy

Fertility in four regions spanning large contrasts in serum levels of widespread persistent organochlorines: a cross-sectional study.

BACKGROUND: Persistent organochlorine pollutants (POPs) may interfere with reproductive function but direct evidence in humans is very limited. METHODS: Fertility was examined in four regions with contrasting blood levels of POPs. Pregnant women and their partners in Warsaw (Poland), Kharkiv (Ukraine) and Greenland were consecutively enrolled during antenatal visits. Swedish fishermen and their spouses were recruited separately and independently of current pregnancy. Lipid adjusted serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (DDE) were available for both partners. Time to pregnancy interviews were obtained among 2269 women and 798 men provided a semen sample. RESULTS: Inuits had high levels of both POP markers, Swedish fishermen were high in CB-153 but low in DDE, men from Kharkiv were high in DDE and low in CB-153 while men from Warsaw were low in CB-153 and had intermediate DDE levels. Compared to Warsaw couples, fecundability was reduced among couples from Kharkiv [adjusted fecundability ratio (FR) 0.64 (95% CI 0.5-0.8)] and elevated in Swedish fishermen families [FR 1.26 (95% CI 1.0-1.6)]. Adjusted geometric means of sperm counts and morphology did not differ between regions while sperm motility was higher in men living in Warsaw. CONCLUSION: We observed regional differences in time to pregnancy and sperm motility that may be related to regional differences in POP blood levels, but other interpretations are also plausible. In particular, differences in access to safe contraception and in the prevalence of contraceptive failures are most likely to bias comparisons of time to pregnancy

The European Registered Toxicologist (ERT) : Current status and prospects for advancement

Acknowledgements We would like to thank the participants of the five workshops in which the issues presented in this paper were discussed and the revised guidelines prepared, as well as the EUROTOX Executive Committee and the societies of toxicology of Sweden, the Netherlands, Switzerland, Austria and France for their support which allowed the workshops to take place.Peer reviewedPostprin